The soft tissues of our bodies connect, support and surround other structures and organs and include connective tissue such as skin, tendons, ligaments, fibrous tissue, fascia, fat and synovial membranes, and non-connective tissue such as muscles, nerves, and blood vessels. Over the course of a person's lifetime, their soft tissues may suffer damage as the result of injury, disease, nutritional deficiencies, toxins, pollutants and other environmental factors, surgical intervention, or simply from wear and tear. Tissue damage can result from many causes, including natural and man-made. A few examples of the common causes of significant tissue damage include traumatic injuries (including lacerations, contusions, abrasions, penetrations, blunt injury or combinations of the foregoing); surgical incisions (such as internal and epidermal surgical incisions); implantation of devices (such as prosthetics and other medical devices); and a variety of other injuries and illnesses.
Injuries to the soft tissue may effect virtually any area of anatomy. For instance, injuries to the soft tissues of the face are particularly conspicuous and include eyelid injuries, ear injuries, nasal injuries, scalp injuries, and lip injuries. Facial and other soft tissue injuries may occur as the result of a wide variety of incidents including motor vehicle accidents, domestic violence, sports, animal bites, self-inflicted wounds, and on-the-job accidents. Injuries to the soft tissue of other areas of the body, though not as conspicuous as those to the face, can cause functional impairment ranging from minor to severe. Tissue damage may result from a variety of surgical techniques including plastic, reconstructive and cosmetic surgery.
Soft tissue damage in human and other mammalian tissue leads to tissue disruption and the coagulation of vasculature at the site of the wound. Our bodies generally react to such tissue damage with a natural cellular response to repair the tissue damage. Soft tissue damage heals in a similar manner regardless of the extent of the damage. Tissue growth and repair involve processes of cellular proliferation and angiogenesis that occurs in the presence of an oxygen gradient. Some of the morphological changes that occur during tissue repair have been characterized. See Hunt, T. K., et al., “Coagulation and macrophage stimulation of angiogenesis and wound healing,” The Surgical Wound, pp. 1-18, (Lea & Febiger, Philadelphia 1981). Tissue regeneration in various organs, such as, for example, the skin or the heart relies upon restoring blood supply to the tissue and allowing cells (for example, keratinocytes or muscle cells) to facilitate organ vitality. One function of mesenchymal cells, such as the fibroblasts or endothelial cells of the vasculature, is secretion of factors enhancing the healing process, such as factors promoting angiogenesis (blood vessel growth) or re-epithelialization.
Skin wounds that do not readily heal can cause the subject considerable physical, emotional, and social distress as well as great financial expense. See e.g., Richey et al., Annals of Plastic Surgery 23(2):159-65 (1989). Wounds that fail to heal properly may require aggressive surgical intervention, such as autologous skin grafting. Even where a wound heals, the anatomy may suffer asthetically or functionally.
Various materials have been proposed for repairing or replacing damaged tissue. For instance, various biomedical applications of collagen, including its use in tissue engineering as a skin replacement, bone substitute, or as artificial blood vessels and valves, are described by Lee et al., “Biomedical applications of collagen”, Intl Journal of Pharmaceutics, 221 (2001) 1-22. The potential use of a polymer material as a patch for rotator cuff repairs is described by Cole et al., “Biocompatibility of a polymer patch for rotator cuff repair”, Knee Surg Sports Traumatol Arthrosc, May 10, 2006.
U.S. Pat. No. 5,922,025 discusses examples of biocompatible materials that have been proposed for use in augmenting soft tissue in the practice of plastic and reconstructive surgery, including collagen, gelatin beads, beads of natural or synthetic polymers such as polytetrafluoroethylene, silicone rubber and various hydrogel polymers, such as polyacrylonitrile-polyacrylamide hydrogels.
Similarly, according to U.S. Pat. No. 4,595,713, a large number of tissue augmentation compositions are proposed, that comprise soft or moldable polymeric materials, which are designed to occupy the space where tissue regeneration is desired, and eventually be replaced by the hard or soft regenerated tissue, such as cartilage or bone. Among the references directed to such invention are U.S. Pat. Nos. 4,424,208 and 4,347,234. The latter, in particular, describes a collagen-based shaped mass which may include osteogenic material, such as tricalcium phosphate. The implant material of both U.S. Pat. Nos. 4,424,208 and 4,347,234 is based on collagen in a binder to form a polymeric mass. U.S. Pat. No. 4,440,750, describes a wide number of compounds found to be osteogenic, and describes a method and preparation for introducing such osteogenic materials where it is necessary to enhance or promote bone regeneration, such as in the case, of genetic disorders and traumatic injury.
A similar material is provided through an alternative approach in U.S. Pat. No. 3,949,073. That patent describes a collagen-based solution which may be injected or implanted into the desired location, and immediately polymerized into a stable mass upon injection. The reference also suggests the use of tissue augmentation materials in addition to the collagen polymer.
A different approach is taken in U.S. Pat. No. 3,919,773, which is directed to a bone replacement, or implant, particularly designed for use in dental or oral surgery, where a socket is exposed after tooth extraction, or an similar void is formed in dental bone. A polymerizable material, comprised, in contrast to U.S. Pat. No. 3,949,073, of synthetic polymers, is injected into the socket and rapidly polymerizes therein, to form a hardened, permanent fixture. To enhance subsequent tissue connection, but not replacement, to the implant, the material, prior to polymerization, is provided with discrete particles that are soluble in body fluids commonly encountered in the oral cavity. When the particles are dissolved, the implant is made porous, which enhances the connection of connective tissue thereto.
Also known in the art are synthetic polymers useful, in general, as surgical articles or devices, owing to their complete bioabsorbability. U.S. Pat. No. 4,243,775 describes a polymer based on lactide and glycolide, which, when polymerized, is designed as a medical suture, or similar sterile surgical article. However, the polymer of the reference is not moldable, and is not suggested as being suitable for the enhancement of, or replacement by, connective tissue.
Other related art also includes a variety of hemostatic materials, designed to control osseous hemorrhage, particularly in the case of orthopedic surgery or the like. Several different compositions are generally described in U.S. Pat. Nos. 4,439,420; 4,440,789 and 4,443,430. Although these compositions may be useful in the healing process, and as an adjunct to surgical or traumatic injury to bone and similar connective tissue, they do not serve as “scaffolds” or similar basis for the replacement of the implant by regenerated tissue, nor do they substantially promote to the regeneration of that tissue.
Most often, the biomaterials are delivered to the tissue site where augmentation is desired by means of an injectable composition which comprises the biomaterial and a biocompatible fluid that acts as a lubricant to improve the injectability of the biomaterial suspension. The injectable biomaterial compositions can be introduced into the tissue site by injection from a syringe intradermally or subcutaneously into humans or other mammals to augment soft tissue, to correct congenital anomalies, acquired defects or cosmetic defects. They may also be injected into internal tissues such as tissue defining sphincters to augment such tissue in the treatment of incontinence, and for the treatment of unilateral vocal cord paralysis.
U.K. Patent Application No. 2,227,176 to Ersek et al, relates to a microimplantation method for filling depressed scars, unsymmetrical orbital floors and superficial bone defects in reconstructive surgery procedures using microparticles of about 20 to 3,000 microns that may be injected with an appropriate physiologic vehicle and hypodermic needle and syringe in a predetermined locus such as the base of depressed scars, beneath skin areas of depression and beneath perichondrium or periosteum in surface irregularities of bone and cartilage. Textured microparticles can be used, including silicone, polytetrafluoroethylene, ceramics or other inert substances. In those instances wherein the requirement is for hard substances, biocompatible material such as calcium salts including hydroxyapatite or crystalline materials, biocompatible ceramics, biocompatible metals such as stainless steel particles or glass may be utilized. Appropriate physiological vehicles have been suggested, including saline, various starches, polysaccharides, and organic oils or fluids.
U.S. Pat. No. 4,803,075 to Wallace et al, relates to an injectable implant composition for soft tissue augmentation comprising an aqueous suspension of a particulate biocompatible natural or synthetic polymer and a lubricant to improve the injectability of the biomaterial suspension. U.S. Pat. No. 4,837,285 to Berg et al, elates to a collagen-based composition for augmenting soft tissue repair, wherein the collagen is in the form of resorbable matrix beads having an average pore size of about 50 to 350 microns, with the collagen comprising up to about 10% by volume of the beads. U.S. Pat. No. 4,280,954 to Yannas et al, relates to a collagen-based composition for surgical use formed by contacting collagen with a mucopolysaccharide under conditions at which they form a reaction product and subsequently covalently crosslinking the reaction product. U.S. Pat. No. 4,352,883 to Lim discloses a method for encapsulating a core material, in the form of living tissue or individual cells, by forming a capsule of polysaccharide gums which can be gelled to form a shape retaining mass by being exposed to a change in conditions such as a pH change or by being exposed to multivalent cations such as calcium. Namiki, “Application of Teflon Paste for Urinary Incontinence-Report of Two Cases”, Urol. Int., Vol. 39, pp. 280-282, (1984), discloses the use of a polytetrafluoroethylene paste injection in the subdermal area to treat urinary incontinence. Drobeck et al, “Histologic Observation of Soft Tissue Responses to Implanted, Multifaceted Particles and Discs of Hydroxylapatite”, Journal of Oral Maxillofacial Surgery, Vol. 42, pp. 143-149, (1984), discloses that the effects on soft tissue of long and short term implants of ceramic hydroxylapatite implanted subcutaneously in rats and subcutaneously and subperiosteally in dogs. The process consisted of implanting hydroxylapatite in various sizes and shapes for time periods ranging from seven days to six years to determine whether migration and/or inflammation occurred. Misiek et al., “Soft Tissue Responses to Hydroxylapatite Particles of Different Shapes”, Journal of oral Maxillofacial Surgery, Vol. 42, pp. 150-160, (1984), discloses that the implantation of hydroxylapatite in the form of sharp edged particles or rounded particles in the buccal soft tissue pouches produced inflammatory response at the implant sites with both particle shapes. Each of the particles weighed 0.5 grams. However, inflammation resolved at a faster rate at the sites implanted with the rounded hydroxylapatite particles. Shimizu, “Subcutaneous Tissue Responses in Rats to Injection of Fine Particles of Synthetic Hydroxyapatite Ceramic”, Biomedical Research, Vol. 9, No. 2, pp. 95-111 (1988), discloses that subcutaneous injections of fine particles of hydroxyapatite ranging in diameter from about 0.65 to a few microns and scattered in the tissue were phagocytized by macrophages in extremely early stages. In contrast, larger particles measuring several microns in diameter were not phagocytized, but were surrounded by numerous macrophages and multinucleated giant cells. It was also observed that the small tissue responses to hydroxyapatite particles were essentially a non-specific foreign body reaction without any cell or tissue damage. R. A. Appell, “The Artificial urinary Sphincter and Periurethral Injections”, Obstetrics and Gynecology Report. Vol. 2, No. 3, pp. 334-342, (1990), is a survey article disclosing various means of treating urethral sphincteric incompetence, including the use of injectables such as polytetrafluoroethylene micropolymer particles of about 4 to 100 microns in size in irregular shapes, with glycerin and polysorbate. Another periurethral injectable means consists of highly purified bovine dermal collagen that is crosslinked with glutaraldehyde and dispersed in phosphate-buffered physiologic saline. Politano et al., “Periurethral Teflon Injection for Urinary Incontinence”, The Journal of Urology, Vol. 111, pp. 180-183 (1974), discloses the use of polytetrafluoroethylene paste injected into the urethra and the periurethral tissues to add bulk to these tissues to restore urinary control in both female and male patients having urinary incontinence. Malizia et al, “Migration and Granulomatous Reaction After Periurethral Injection of Polytef (Teflon)”, Journal of the American Medical Association, Vol. 251, No. 24, pp. 3277-3281, Jun. 22-29 (1984), discloses that although patients with urinary incontinence have been treated successfully by periurethral injection of polytetrafluoroethylene paste, a study in continent animals demonstrates migration of the polytetrafluoroethylene particles from the inspection site. Claes et al, “Pulmonary Migration Following Periurethral Polytetrafluoroethylene Injection for Urinary Incontinence”, The Journal of Urology, Vol. 142, pp. 821-2, (September 1989), confirms the finding of Malizia in reporting a case of clinically significant migration of polytetrafluoroethylene paste particles to the lungs after periurethral injection. Ersek et al, “Bioplastique: A New Textured Copolymer Microparticle Promises Permanence in Soft-Tissue Augmentation”, Plastic and Reconstructive Surgery, Vol. 87, No. 4, pp. 693-702, (April 1991), discloses the use of a biphasic copolymer made of fully polymerized and vulcanized methylmethylpoly-siloxane mixed with a plasdore hydrogel, and used in reconstructing cleft lips, depressed scars of chicken pox and indentations resulting from liposuction, glabella frown wrinkles and soft tissue augmentation of thin lips. The biphasic copolymer particles were found to neither migrate nor become absorbed by the body were textured and had particle sizes varying from 100 to 600 microns. Lemperle et al. “PMMA Microspheres for Intradermal Implantation: Part I. Animal Research”, Annals of Plastic Surgery, Vol. 26, No. 1, pp. 57-63, (1991), discloses the use of polymethylmethacrylate microspheres having particle sizes of 10 to 63 microns in diameter used for correction of small deficiencies within the dermal corium to treat wrinkles and acne scars. Kresa et al, “Hydron Gel Implants in Vocal Cords”, Otolaryngology Head and Neck Surgery, Vol. 98. No. 3, pp. 242-245, (March 1988), discloses a method for treating vocal cord adjustment where there is insufficient closure of the glottis which comprises introducing a shaped implant of a hydrophilic gel that has been previously dried to a glassy, hard state, into the vocal cord. Hirano et al, “Transcutaneous Intrafold Injection for Unilateral Vocal Cord Paralysis: Functional Results”, Ann Otol. Rhinol. Laryngol., Vol. 99, pp. 598-604 (1990), discloses the technique of transcutaneous intrafold silicone injection in treating glottic incompetence caused by unilateral vocal fold paralysis. The silicone injection is given under a local anesthetic with the patient in a supine position, wherein the needle is inserted through the cricothyroid space. Hill et al, “Autologous Fat Injection for Vocal Cord Medialization in the Canine Larynx”, Laryngoscope, Vol. 101, pp. 344-348 (April 1991), discloses the use of autologous fat as an alternative to TEFLON. collagen as the implantable material in vocal cord medialization, with a view to its use as an alternative to non-autologous injectable material in vocal cord augmentation. Mikaelian et al, “Lipoinjection for Unilateral Vocal Cord Paralysis”, Laryngoscope, Vol. 101, pp. 4654-68 (May 1991), discloses that the commonly used procedure of injecting TEFLON paste to improve the caliber of voice in unilateral vocal cord paralysis has a number of drawbacks, including respiratory obstruction from overinjected TEFLON and unsatisfactory voice quality. In this procedure, lipoinjection of fat commonly obtained from the abdominal wall appears to impart a soft bulkiness to the injected cord while allowing it to retain its vibratory qualities. The injected fat is an autologous material which can be retrieved if excessively overinjected. Strasnick et al, “Transcutaneous Teflon Injection for Unilateral Vocal Cord Paralysis: An Update”, Laryngoscope, Vol. 101, pp. 785-787 (July 1991), discloses the procedure of TEFLON injection to restore glottic competence in cases of paralytic dysphonia.
Many previously attempted materials for tissue augmentation, repair or replacement are unsuitable for a variety of reasons including efficacy, lack of biocompatibility, expense, and ease of use. For example, collagen, being an organic substance principally derived from bovines, presents potentially serious allergenic reaction problems, and general difficulties with a patient's immune system. Further, it is difficult to insure the sterility of collagen, and the storage requirements associated with it are quite extensive, and expensive. Many previously used materials lack the mechanical strength and/or flexibility to be useful in tissue repair and/or replacement. Many materials also deteriorate fairly quickly and therefore do not present a viable long term treatment option.
There remains an ongoing need for treatments and materials to repair and/or replace tissue that is damaged (for asthetic, structural and/or functional purposes), or provide post-surgical augmentation of tissue, including treatments in which the damaged tissue is supplemented, partially replaced or entirely replaced. Further, there is a demand for a durable, long-lasting, biocompatible approach that restores the asthetic appearance of the tissue and/or restores the normal physiological function of the tissue including providing or improving function, movement, balance and support.